PXD004169-1

PXD004169 is an original dataset announced via ProteomeXchange.

Title	Gadd45a Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4
Description	Skeletal muscle atrophy is a serious and highly prevalent condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves an increase in skeletal muscle Gadd45a expression, which is necessary and sufficient for skeletal muscle fiber atrophy. However, the direct mechanism by which Gadd45a promotes skeletal muscle atrophy was unknown. To address this question, we biochemically isolated skeletal muscle fiber proteins that associate with Gadd45a as it induces skeletal muscle atrophy in living mice. We found that Gadd45a interacts with multiple proteins in skeletal muscle fibers, including, most prominently, the MAP kinase kinase kinase MEKK4. Furthermore, by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is sufficient to induce skeletal muscle fiber atrophy and required for Gadd45a-mediated skeletal muscle fiber atrophy. Together, these results identify a direct biochemical mechanism by which Gadd45a induces skeletal muscle atrophy and provide new insight into way that skeletal muscle atrophy occurs at the molecular level.
HostingRepository	MassIVE
AnnounceDate	2016-07-11
AnnouncementXML	Submission_2016-07-11_15:08:34.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Birgit Schilling
SpeciesList	scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationList	Phospho
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2016-05-17 22:25:09	ID requested
⏵ 1	2016-07-11 15:08:36	announced

Bullard SA, Seo S, Schilling B, Dyle MC, Dierdorff JM, Ebert SM, DeLau AD, Gibson BW, Adams CM, Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4. J Biol Chem, 291(34):17496-17509(2016) [pubmed]

submitter keyword: Gadd45a, Muscle Atrophy, Protein Kinase MEKK4

Christopher M. Adams
lab head
Birgit Schilling
contact affiliation	Buck Institute
contact email	bschilling@buckinstitute.org
dataset submitter

MassIVE dataset URI

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